doi:10.1016/j.jcms.2006.10.003, available online athttp://www.sciencedirect.com
Inverted papilloma of paranasal sinuses
Georg EGGERS1, Joachim MU¨HLING1, Stefan HASSFELD2
1Department of Oral and Cranio-Maxillofacial Surgery, Heidelberg University Hospital (Head: Prof. Dr. Dr.
Joachim Mu¨hling), Heidelberg, Germany;2Department of Oral and Cranio-Maxillofacial Surgery, Klinikum Dortmund (Head: Prof. Dr. Dr. Stefan Hassfeld), Germany
Available online 30 January 2007
SUMMARY. Introduction: Inverted papilloma (Schneiderian papilloma) is a primarily benign lesion that occurs in the nasal cavity and paranasal sinuses. Clinical problems include a tendency towards local destruction, recurrence and malignant transformation into squamous cell carcinoma. Hence, complete surgical removal is the therapy of choice and a meticulous follow-up is mandatory. Study design: This is a review including a short introduction to the different histological types of nasal papilloma, their pathogenesis and the clinical and histopathological diagnosis. Staging systems, therapeutic approaches, and surgical concepts are discussed.
Result: The detection and definition of factors that allow a prognosis of recurrence or malignant transformation of inverted papilloma is an active field of research. The results of studies dealing with the definition of prognostic factors, that investigated immunohistochemical methods, virus detection, molecular genetics, and histomorpholo- gical studies are discussed including our own results on the prognostic value of histology. A concept for the diagnosis, management, therapy and follow-up of inverted papilloma is proposed. r 2006 European Association for Cranio-Maxillofacial Surgery
Keywords: papilloma; inverted; paranasal sinus
HISTORY AND CLASSIFICATION OF NASAL PAPILLOMA
The nomenclature of nasal papilloma is manifold.
The first description of this entity by Ward (1854) described the macroscopic aspect of a papillomatous neoplasm. The name ‘villous carcinoma’ for the same entity (Billroth, 1855) described the tendency to recur and grow. Hopmann (1883) differentiated hard and soft papilloma. He assessed the stroma–epithelium ratio. This, however, proved to be of limited value, since the number of epithelial cell layers varied within the same specimen and made an unambiguous classification impossible. Ringertz (1938) recognized the characteristic endophytic growth pattern and coined the term ‘inverting papilloma’. Synonyms for the same entity were ‘genuine papilloma of the nasal cavity’ (Kramer and Som, 1935), ‘inverting papilloma’
(Norris, 1963), and ‘inverted papilloma’ (Fechner and Alford, 1968; Hyams, 1971). Berendes (1966) noted the tendency towards destructive growth, recurrence, and epithelial metaplasia and named it ‘malignant papilloma’. However, this term is misleading since papilloma lacks the essential criteria for malignancy, such as metastasis. In a groundbreaking study, Hyams (1971) classified papillomas due to their pattern of growth. Papillomas with endophytic growth were classified as inverted papilloma (IP), papillomas with exophytic growth as fungiform papilloma. The third group were cylindrical cell papilloma. The WHO classification basically fol- lowed this classification (Shanmugaratnam and Sobin,
1991). However, many synonyms are still in current use (Batsakis, 1987). In the English-speaking area, it is also called ‘inverted Schneiderian papilloma’, indicating its origin from the Schneiderian membrane (Vrabec, 1994; Ganzer et al., 1992). It should be noted, that some authors regard the three types of nasal papilloma as three completely distinct entities (Michaels, 1996), while others confirm, that there are hybrid lesions combining features of IP and cylind- rical cell papilloma in just one lesion (Hyams, 1971;
Kaufman et al., 2002;Eggers et al., 2005).
DEFINITION OF INVERTED PAPILLOMA IP of the nose and paranasal sinuses is a primary benign epithelial tumour. Its share of all tumourous lesions of the nose and paranasal sinuses is 0.5–5%
(Batsakis, 1987;Lantis et al., 1968;Maran and Lund, 1990).
The typical histopathological feature is inversion of the multilayer epithelium into the underlying oede- matous stroma. Squamous cell epithelium is fre- quently found, but there is also transitional cell epithelium, cylinder cell epithelium, or combinations of these. The basement membrane is typically intact.
Stroma is well vascularized and infiltrated with lymphocytes and plasma cells (Hyams, 1971).
IP occurs predominantly in male patients. Most authors stated a male/female ratio of 3:1 (Hyams, 1971; Beck et al., 1984; Nielsen et al., 1991;
Dolgin et al., 1992; Peter and Grossenbacher, 1997;
21
Plinkert et al., 1997). Some authors state a higher rate of male patients (Maran and Lund, 1990;Myers et al., 1981). IP typically occurs between the second and eighth decade of life, with a peak around the age of 50 (Ridolfi et al., 1977; Dolgin et al., 1992). Cases of sinonasal papilloma in children have been described byMaran and Lund (1990).
Aetiology
Little is known about the aetiology of IP. Molecular- genetic investigations have shown that it is a neoplasm arising from a single progenitor cell (Califano et al., 2000).
A possible viral aetiology has been the focus of many studies. Papovavirus-DNA was found (Siivonen and Virolainen, 1989), but the main focus is on Human Papilloma Virus (HPV) which is suspected to be associated with the formation of IP, since HPV-DNA was found in IP. Different patterns of HPV-subtypes were found (Beck et al., 1995b), but HPV-DNA could not be found in all samples of IP tissue. On the one hand this might be due to the fact that sometimes old samples were investigated, where the DNA had already been degraded (Arndt et al., 1994;Kashima et al., 1992). On the other hand there might be other causes for IP (Syrja¨nen 2003). Chronic inflammation has been associated with the genesis of IP (Vrabec, 1994) as well as occupational exposure to different smokes, dusts, and aerosols (Deitmer and Wiener, 1996).Dictor and Johnson (2000) found an association of IP with non-sinonasal head and neck cancer and hence suspected tobacco as the causative link.
Clinical presentation
Typically, IP occurs unilaterally. Bilateral growth is only described in approximately 5% of the cases. The most frequent location (80%) is the lateral wall of the nasal cavity in the region of the root of the middle turbinate. Proximity to the nasal septum is much less frequent (Batsakis, 1980, 1987;Majumdar and Beck, 1984;Myers et al., 1990;McCary et al., 1994;Lawson et al., 1995). In the nose and paranasal sinuses, IP occurs only in areas with mucosa of ectodermal origin (Arndt et al., 1994).
Case history and symptoms
Symptoms and case histories of patients suffering from IP are non-specific. Some patients report a history of nasal polyposis with repeated polypectomy or paranasal sinus surgery (Batsakis, 1987). However, there is no increased rate of IP in patients with recurrent nasal polyposis (Garavello and Gaini, 2006).
Typical complaints are nasal obstruction, hypoosmia, frontal headache, epistaxis and rhinorrhoea (Buchwald et al., 1989; 1995b). Rarely occurring symptoms are tinnitus, sensorineural hearing loss, diplopia or meningitis (Granet et al., 1996; Eisen et al., 2002; Lee et al., 2003). The duration of symptoms is highly variable, between 0 and 72 (Christensen and Smith, 1986) or even up to 120 months (Myers et al., 1981) with an average of 24 months (Buchwald et al., 1989). In our cohort of 93 patients (Table 1), it was found that nasal obstruction was the most frequent, (yet non-specific) symptom. It has, however, to be noted that some of the patients with IP or a recurrence of IP were totally asympto- matic. Furthermore, even patients with carcinoma in IP could be completely free of symptoms.
Diagnostics
Early diagnosis of IP is essential for optimum management. Hence, the clinician should have a low threshold for suspecting the disease (Lund, 2000).
Clinical Examination
The best means of examination is nasal endoscopy.
The macroscopic appearance has been described as that of a tumour with a mulberry-like uneven surface and a grey-livid colour (Ganzer et al., 1992) but other colours can be encountered as well.
Imaging
Typical findings on plain radiographs, tomography, or CT scan are a unilateral opacification of the maxillary or ethmoid sinus and a mass in the nasal fossa. Other findings can be thinning or destruction of the bony lateral nasal wall, as well as decalcifica- tion or deformation. Unilateral opacification of the contiguous maxillary sinus is a common finding but there is no specific radiological appearance of IP.
Table 1 – Frequency of symptoms prior to diagnosis in 93 patients with an inverted papilloma (IP; all values: Percentage of all patients within the respective group)
Symptom Primary Diagnosis IP (%) Recurrence of IP (%) Carcinoma in IP (%)
(n ¼ 68) (n ¼ 13) (n ¼ 12)
Nasal obstruction 82 62 75
Rhinorhoea 19 23 0
Impaired sense of smell 18 0 17
Pain 12 0 17
Feeling of pressure 7 15 8
Epistaxis 9 0 25
Diplopia 4 0 8
None 6 23 8
Angiography is of limited use since it is a relatively avascular tumour. Furthermore, ultrasound and radionuclide scanning have not been found to be useful (Momose et al., 1980).
CT-imaging is the modality of choice (Lund and Lloyd, 1984). However, due to its poor soft tissue contrast, the tumour cannot be differentiated from retained secretion or inflammation in CT. Hence the size of an IP may be exaggerated by CT (Lund, 2000).
Steroids and antibiotics applied prior to imaging can reduce concomitant inflammatory polyps to avoid overestimation of the disease mass (Kraft et al., 2003). Strictly unilateral opacification of paranasal sinuses is a warning sign of the presence of IP (Fig. 1) but since there are no definite diagnostic criteria, the role of imaging is just for preoperative staging of an otherwise confirmed IP (e.g. by means of biopsy).
A tumour of convoluted cerebriform appearance in T2-weighted or enhanced T1-weighted MRIs, located in the maxillary sinus and middle nasal meatus, is suspicious of IP. Central necrosis could be a sign of associated malignancy (Ojiri et al., 2000). Further- more, inflammation or retained secretion can be identified in MRI (Lund, 2000). Hence, with MRI the tendency to overestimate the size of IP is less than with CT (Oikawa et al., 2003).
Histology
The definite diagnosis of IP can only be made by histology. Haematoxylin–eosin staining of a speci- men obtained by transnasal biopsy under local anaesthesia is routine. Diagnosis of IP can also be performed using fine needle aspiration (Bocklage and Herzon, 1994;Gould et al., 2004).
Laboratory
There is no specific tumour marker for IP.Yasumatsu et al. (2002)found elevated serum levels of squamous
cell antigen (SCCA1) in 91% of IP cases, decreasing after resection. SCCA1 was overexpressed in IP tissue but not in SCC or normal tissue. However, this data is not yet confirmed in routine clinical practice.
Clinical problems in the management of IP
There are three clinical problems that require particular attention in the management of IP: local destruction of bone, a tendency to recur, and associated malignancy (Lawson et al., 1989).
Local bone destruction
IP will displace neighbouring structures. The pressure of the growing IP causes also erosion of bone. In the event of osteolysis the presence of associated malig- nancy has to be considered (Batsakis, 1980).
Recurrence
The frequency of recurrence after surgical removal is reported as 28–74% (Alford and Winship, 1963;
Norris, 1963; Hyams, 1971; Snyder and Perzin, 1972; Batsakis, 1987; Ganzer et al., 1992). The observation that IP tends to recur after incomplete surgical removal supports investigations suggesting that IP is a true neoplasm arising from a single progenitor cell and that recurrence represents growth of the residual clone (Califano et al., 2000).
Some authors assume that HPV subtyping enables a prognosis of the probability of recurrence. Beck et al. (1995a)found that patients with proof of HPV types 6 or 11 have a lower rate of recurrence than patients with HPV types 16 or 18.
Associated malignancy
Carcinoma occurs with IP (synchronous carcinoma) or at a later time (metachronous carcinoma). The majority of cases in the literature are synchronous carcinomas (Myers et al. 1990; Dolgin et al., 1992;
Lawson et al., 1995). However,Christensen and Smith (1986) found equal numbers of synchronous and metachronous carcinomas.
Cases of verrucous carcinoma (Orvidas et al., 1999) or adenocarcinoma (Buchwald et al., 2001) have also been reported, but the associated malignancy is predominantly squamous cell carcinoma (SCC).
Sinonasal SCC associated with IP has an incidence of approx. 0.38 cases/million persons/year (Buchwald et al., 2001). The frequency of carcinoma in patients with IP is reported to be 1–53% (Hyams, 1971;
Calcaterra et al., 1980; Lawson et al., 1989; Myers et al., 1990; Dolgin et al., 1992; Lesperance and Esclamado, 1995; Lawson et al., 1995; Peter and Grossenbacher, 1997). This considerable variation results from different follow-up periods and cohort sizes (Arndt et al., 1994). There are many reports of a change from primarily benign IP to carcinoma in situ and to invasive carcinoma (Marcial-Rojas and De Leon, 1963; Mabery et al., 1965). Patients with carcinoma in IP are older than those IP patients without carcinoma (Myers et al., 1981; Christensen
Fig. 1 – Typical CT findings (coronal image) in a male patient with inverted papilloma: unilateral opacification of the paranasal sinuses on the right caused by the papilloma. It cannot be differentiated from obstructed secretions or nasal polyps.
and Smith, 1986; Lesperance and Esclamado, 1995) and predominantly male (Lesperance and Esclamado, 1995;Buchwald et al., 1995b).
The cause of development of a carcinoma in the IP has not yet been identified. Cytokeratin 5 and cytokeratin 13 have been found to be elevated in IP compared with normal epithelium (Plinkert et al., 1997). While molecular genetic investigations show that IP is a neoplasm arising from a single progenitor cell, IP is not necessarily premalignant. Squamous cell dysplasia, the precursor of SCC, exhibits specific genetic alterations in the first stages, before develop- ment of morphological features. In contrast, IP does not accumulate key genetic alterations of head and neck squamous cell carcinoma (loss of heterozygosity on chromosomes 3p, 9p, 11q, 13q, 17p; Califano et al., 2000). Key genetic alterations are present in squamous epithelial dysplasia, even in the earliest stages of tumour progression (Califano et al., 1996).
Mutation of the p53 tumour suppressor gene was named as a risk factor for malignant transformation (Caruana et al., 1997) and elevated levels of epithelial growth factor receptor (EGFR) and TGF-alpha were found in precancerous IP-lesions (Katori et al., 2005).
Some authors assume an influence of HPV subtyping. Transcripts of HPV DNA were found in malignant IP (McKay et al., 2005).Beck et al. (1995b) found that patients with HPV types 6 or 11 have a lower rate of associated malignancy than patients with HPV types 16 or 18. However, other authors did not find a correlation between development of malignancy in IP and proof of HPV (Buchwald et al., 1995a;Kraft et al., 2001).
Therapy Surgery
Complete surgical removal is the first option for the treatment of IP and is superior to radiation or chemotherapy (Ganzer et al., 1992; Lund, 2000).
Removal should be complete to avoid recurrence (Thorp et al., 2001). The extent of the disease should be determined preoperatively by CT-imaging (Myers et al., 1990) or MRI for proper planning.
A variety of surgical techniques has been devel- oped. Radical transfacial approaches like lateral rhinotomy, minimally invasive transnasal endoscopic techniques, and anything in between including mid- face degloving procedures are in use for the treatment of IP. The aim of surgery must always be the eradication of the disease at the first attempt (Han et al., 2001). The recurrence rate increases markedly if there was inadequate removal in the first place (McCary et al., 1994). Another important goal of surgery is to have an anatomically clear situation postoperatively allowing the site to be properly monitered at follow-up (Delank et al., 2000).
Lateral rhinotomy has been regarded as the traditional standard surgical approach to control IP and to avoid recurrence (Myers et al., 1981). It gives a good overview and wide access to the surgical field
and can also be performed bilaterally (Hosal and Freeman, 1996). However, side-effects of this proce- dure may be epiphora, chronic dacryocystitis, tran- sient diplopia, Eustachian tube dysfunction and facial scarring (Tomenzoli et al., 2004). Lateral rhinotomy was found to be associated with fewer recurrences and a better probability of cure than other ap- proaches (Weissler et al., 1986).
Alternative techniques have been sought to avoid the facial scarring. The midface degloving procedure (Casson et al., 1974) as an alternative access has been further modified depending on the extent of disease (Fliss et al., 2000; Jeon et al., 2003). Midfacial degloving gives a good intraoperative view and wide access to bilateral IP (Buchwald et al., 1995b). Some authors recommend Denker’s approach for good access without a facial skin incision (Sanderson and Knegt, 1999). However, less aggressive non-endo- scopic access to the sinuses such as Caldwell–Luc’s approach have been associated with high recurrence rates (Krouse, 2001).
The most recent developments in surgery are minimally invasive transnasal endoscopic techniques (Winter et al., 2000;Wormald et al., 2003).Waitz and Wigand (1992) first reported a series of patients in whom the recurrence rate was not worse when compared with open access (17% vs. 19%). Other reports on similar results of endoscopic surgery followed (Buchwald et al., 1989; McCary et al., 1994; Han et al., 2001).
The technical advantage of endoscopy can be a multi-angled magnified view making differentiation of diseased and normal mucosa easier (Tomenzoli et al., 2004). However, in the case of frontal sinus involvement, a combined approach is necessary even though endoscopic techniques are improving (Chandra et al., 2004). The piecemeal approach, inherent with endoscopic surgery, could be acceptable because what is most important is to identify and widely remove the site of attachment (Han et al., 2001; Kraft et al., 2003). Recently, the use of navigation systems for endoscopic removal of IP has been reported (Von Buchwald and Larsen, 2005) but recurrences were still reported.
The question as to whether endoscopic treatment is as safe as open surgical access, is ongoing in the (scientific) literature. In endoscopically accessible locations, recurrence rates for endoscopic vs. open surgery were similar (Klimek et al., 2000). However, other studies reported higher recurrence rates of IP (Phillips et al., 1990), particularly in cases of peripheral extension, especially into the maxillary sinus (Zumegen et al., 2000).
A possible reason for these differences could be different patient selection criteria. In a retrospective review,Krouse (2001)found low recurrence rates with endoscopic surgery, but conceded the probability of a bias in patient selection by the surgeon. Since endoscopic resectability depends on location and extent of the tumour, the external approaches are commonly used to avoid incomplete resection and recurrence in patients in whom the disease extended
towards the periphery of the paranasal sinuses or beyond. In cases of malignancy, en-bloc resection is the method of choice (Krouse, 2001). Other contra- indications for endoscopic surgery are extensive erosion of the skull base, extensive involvement of the frontal sinus, or scarring (Tomenzoli et al., 2004).
As a consequence of these difficulties and differ- ences it appears necessary to develop a reproducible staging of the patients in order to allow proper comparison of the different treatment options. A number of staging systems for diseases of the nose and paranasal sinuses have already been suggested.
Staging
There is a variety of systems for staging inflammatory sinus disease (Friedman et al., 1990; Kennedy, 1992;
Lund and MacKay, 1993) and also for staging of carcinoma of the paranasal sinuses (Carinci et al., 1966; Greene et al., 2002). Systems have also been developed for staging IP (Skolnik et al., 1966;
Schneider, 1976). These systems propose four stages, with the disease confined to the nose as T1, disease outside the nose or paranasal sinuses as T4. Based on the involvement of paranasal sinuses, intermediate levels are staged as T2 or T3. The more advanced the disease, the higher the stage. However, for the assessment of resectability of the disease, the difficul- ties encountered during the operation should also be considered (Krouse, 2000). IP that arise from the lateral or inferior maxillary sinus are more difficult to remove endoscopically and are more likely to recur than IP, which is sessile on medial parts of the maxillary sinus (Stankiewicz and Girgis, 1993). Hence Waitz and Wigand (1992)recommended the external approach for those IP growing from peripheral regions of the sinuses.
This important difference in location was not considered by most of the existing staging systems.
Hence, another staging system for IP was introduced considering the specific difficulties of endoscopic surgery of IP (Table 2; Krouse, 2000). The intention was to allow an assessment of outcome following different approaches. Standardized grouping of IP is necessary to allow valid studies or meta-analysis (Han et al., 2001). To date, there are no prospective long- term studies with sufficiently large cohorts of equivalently staged patients. Hence, the definite role of therapeutic endoscopy has yet to be determined.
Today, there is no single right or wrong method, but a range from which to choose in the individual case.
The optimum surgical approach is determined by the extent of disease. Other factors in the choice of surgery are the surgical expertise, particularly in endoscopic IP surgery (Lane and Bolger, 2006),
previous treatment, and individual patient factors (Lund, 2000).
Radiotherapy
There are no comparative data for radiotherapy and surgery for the treatment of IP. Few reports have been published with only small cohorts of patients who underwent radiotherapy for the treatment of IP.
Furthermore, in most of these cases, IP was associated with a malignancy, was inoperable or was a recurrence (Mendenhall et al., 1985; Weissler et al., 1986; Guedea et al., 1991; Hug et al., 1993;
Gomez et al. 2000). Also, some of the cases had been treated with a combination of surgery and radio- therapy. Some authors recommended radiotherapy as an adjunct to surgical therapy in cases with asso- ciated malignancy or when complete resection was impossible (Lawson et al., 1995;Dolgin et al., 1992).
Chemotherapy
Reports about chemotherapy for IP are rare and always related to cases with associated malignancy (Podd et al., 1994). Not a single publication was found on chemotherapy for IP without malignancy.
Postoperative management
The tendency to recur and the associated malignancy warrant meticulous follow-up of patients with IP. A good field of view of the affected region is essential (Dolgin et al., 1992). This should be considered during surgery (Delank et al., 2000). Long-term follow-up is necessary as recurrence may occur even after several years (Winter et al., 2000; Eggers et al., 2005).
The diagnosis of recurrence is based on endoscopy, CT imaging and biopsies (Lenders et al., 1994). Some authors recommend follow-up CT scans after surgery (Lesperance and Esclamado, 1995). MR imaging has also been suggested as a follow-up technique to discriminate recurrent tumour from postoperative change and to identify optimum sites for control biopsy (Lai et al., 1999;Petit et al., 2000).
Whilst recurrence of IP is not necessarily asso- ciated with any symptom (Eggers et al., 2005), it would be advantageous for further progress of a patient to identify prognostic factors.
Prognostic factors
A variety of prognostic factors have been suggested for IP.
Table 2 – Characterisitcs of the staging system for inverted papilloma (IP) as suggested byKrouse (2000) T1 IP confined to nasal cavity. No malignancy
T2 IP limited to ethmoid sinus and to medial and superior parts of the maxillary sinus. No malignancy
T3 IP extends into frontal or sphenoid sinuses or involves inferior or lateral parts of maxillary sinus. No malignancy T4 IP associated with malignancy – or IP spreads outside the nose and paranasal sinuses with or without malignancy
Tumour size
Lawson et al. (1995)reported that the only prognostic factor for recurrence was the size of the tumour.
However, it remains unclear whether he observed real recurrence or incomplete removal of the lesion.
Virus
The importance of human papilloma virus (HPV) and its subtypes is not clear yet. High- and low-risk- associated HPV types are known for other disorders.
This was also claimed for IP, with HPV 6 and 11 as low-risk- and HPV 16 and 18 as high-risk-types (Arndt et al., 1994), while other authors reject HPV screening as not being useful as a prognostic parameter (Kraft et al., 2001). Furthermore, the overall detection rate of HPV in IP varies consider- ably, between 24% (Kashima et al., 1992) and 63%
(Beck et al. 1995a). In a meta-analysis, Syrja¨nen (2003) found HPV 6 and 11 in 33.3% of all benign sinonasal papillomas, whereas 21.7% of all sinonasal carcinomas contained HPV 16 and 18. This author concluded that sinonasal SCC could be seen as an emerging HPV lesion, but still conceded the possibi- lity, that the aetiology of sinonasal papillomas and carcinomas is heterogeneous.
Histopathological criteria Epithelium
Various studies have been performed in order to derive prognostic factors from the histopathological examination of IP tissue.Kaufman et al. (2002)found an increased rate of recurrence and malignancy for papilloma with cylindrical cell epithelium. This finding could not be confirmed by own investigations (Eggers et al., 2005). Luhn and Ho¨rmann (1987) grouped IP into a ‘solitary nodal IP’ with a nodular smooth surface, a ‘multilocular nodular IP’ with verrucous flat growth, and a ‘myxoid IP’, forming masses in the nasal cavity. The first two groups were found on the nasal septum, while the latter was found on the lateral wall of the nasal cavity and in the paranasal sinuses. Only this last subtype showed malignant transformation in that study. However, cases of multilocular nodular IP and solitary nodal IP with a malignant transformation have also been reported (Eggers et al., 2005).
Buchwald et al. (1989) classified IP according to their epithelium: squamous cell epithelium, metaplas- tic epithelium and glandular epithelium, as well as combinations of these. There was no coherence between clinical course (recurrence, malignant trans- formation) and histological classification (type of epithelium, frequency of mitosis). Batsakis and Suarez (2001) suggested that ‘obvious keratosis’
might be an ‘ominous sign’ but they conceded that there was no strong predictive factor from histology.
Subtyping into hard and soft papilloma due to the ratio of stroma:epithelium (Kramer and Som, 1935) did not show any correlation with the prognosis
(Eggers et al., 2005), nor did a classification relating to infiltration or eosinophilia.
Cellular changes
Snyder and Perzin (1972)related cellular atypia to an increased incidence of recurrence of IP. An increased rate of mitoses or dyskaryoses in IP was the only parameter associated with an increased rate of malignant transformation in the study by Eggers et al. (2005). However,Lawson et al. (1995)found no coherence between cellular atypia and recurrence. In essence, there is no reliable parameter for the prognosis of recurrence or malignant transformation of a diagnosed IP yet.
This does not have any negative consequences for patients with synchronous SCC, because malignant transformation has already occurred and will be diagnosed by routine histopathology examination. In all other cases these parameters might help to identify a group with a high risk for metachronous SCC that needs particular attention in follow-up.
CONCLUSION
Inverted papilloma (IP) is a true neoplasm having a possible association with HPV infection, but the aetiology is not yet fully understood. The disease has no typical symptoms, no typical history or radiolo- gical findings. Key features are the local destruction of bone, the tendency to recur, and the association with malignancy.
It is important to consider the possibility of IP in patients with unclear nasal symptoms that last longer than one month. Furthermore, in case of a unilateral opacification of the sinonasal system in CT-imaging, a biopsy should be performed, if no firm alternative diagnosis can be reached.
Definite diagnosis is possible only by histological examination. This warrants the routine examination of all tissues surgically removed from the nose!
IP should be removed completely at the first operation. Minimally invasive endoscopic surgery has been introduced successfully for the management of IP, but there is a lack of data to assess the outcome of this method in comparison with conventional open surgery.
Long-term follow-up is necessary. Older male patients at the time of first diagnosis, patients with increased mitoses or atypia of nuclei in histological examination, and patients having undergone the resection of a large papilloma seem to be at higher risk and need particular attention. However, no reliable factors for the prognosis is known as of today. Hence, meticulous follow-up is mandatory.
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Priv.-Doz. Dr. med. Dr. med. dent. Georg EGGERS Department of Oral and Cranio-Maxillofacial Surgery Im Neuenheimer Feld 400 69120
Heidelberg, Germany Tel.: +49 6221 56 73 32 Fax: +49 6221 56 42 22
E-mail:georg.eggers@med.uni-heidelberg.de Paper received 9 November 2004
Accepted 17 October 2006
